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At least 505 records · Page 28Linked to original sources
PubMed2005

CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration.

The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 (CD66a) and the scaffolding protein filamin A have both been implicated in tumor cell migration. In the present study we identified filamin A as a novel binding partner for the CEACAM1-L cytoplasmic domain in a yeast two-hybrid screen. Direct binding was shown by surface plasmon resonance analysis and by affinity precipitation assays. The association was shown for human and rodent CEACAM1-L in endogenous CEACAM1-L expressing cells. To address functional aspects of the interaction, we used a well-established melanoma cell system. We found in different migration studies that the interaction of CEACAM1-L and filamin A drastically reduced migration and cell scattering, whereas each of these proteins when expressed alone, acted promigratory. CEACAM1-L binding to filamin A reduced the interaction of the latter with RalA, a member of the Ras-family of GTPases. Furthermore, co-expression of CEACAM1-L and filamin A led to a reduced focal adhesion turnover. Independent of the presence of filamin A, the expression of CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered cytoskeletal rearrangements during monolayer wound healing assays. Together, our data demonstrate a novel mechanism for how CEACAM1-L regulates cell migration via its interaction with filamin A.

Animals↗
PubMed1979

On the progenitor cell migration velocity.

An attempt is presented to extract cell kinetic information from histomorphological features. It is applicable to rapidly proliferating tissues like the intestinal epithelium. Each replicating tissue has an origin where cells are formed and a periphery toward which cells migrate. The migration path along which they move is denominated as tissue radius on which all cell positions are mapped. Cell migration on the radius is associated with cell proliferation at tissue origin. Each mitosis there is associated with the displacement of all cells distal to it by one cell position. The more mitoses positioned between a cell and tissue origin, the greater its migration velocity. It is possible therefore to derive the cell migration velocity v(x) from the cumulative mitotic distribution on the radius, N(x). v(x) = N(x)/tm (tm = mitotic time). In this form v(x) represents also cell production at any point on the radius and may serve for the computation of other cell kinetic parameters like generation time. These arguments are illustrated on the rat incisor tooth inner enamel epithelium which has been studied in the normal and rapidly erupting tooth.

Ameloblasts↗
PubMed2004

A role for JNK-paxillin signaling in cell migration.

Recently, we and others demonstrated that JNK is essential for cell migration in a number of cell types. We also showed that JNK phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in vivo. Moreover, phosphorylation of Ser 178 on paxillin is essential for cell migration and involved in modulating cell adhesions. A model is proposed to depict the role of JNK-paxillin signaling in cell migration.

Animals↗
PubMed2003

PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration.

This study was designed to identify the molecular mechanisms of phosphatidylinositol 3-kinase (PI3K)-induced actin filament remodeling and cell migration. Expression of active forms of PI3K, v-P3k or Myr-P3k, was sufficient to induce actin filament remodeling to lead to an increase in cell migration, as well as the activation of Akt in chicken embryo fibroblast (CEF) cells. Either the inhibition of PI3K activity using a PI3K-specific inhibitor, LY-294002, or the disruption of Akt activity restored the integrity of actin filaments in CEF cells and inhibited PI3K-induced cell migration. We also found that expression of an activated form of Akt (Myr-Akt) was sufficient to remodel actin filaments to lead to an increase in cell migration, which was unable to be inhibited by the presence of LY-294002. Furthermore, we found that p70S6K1 kinase was a downstream molecule that can mediate the effects of both PI3K and Akt on actin filaments and cell migration. Overexpression of an active form of p70S6K1 was sufficient to induce actin filament remodeling and cell migration in CEF cells, which requires Rac activity. These results demonstrate that activation of PI3K activity alone is sufficient to remodel actin filaments to increase cell migration through the activation of Akt and p70S6K1 in CEF cells.

Actin Cytoskeleton↗
PubMed2006

Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration.

Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders.

Aging↗
PubMed1992

Vital dye analysis of cranial neural crest cell migration in the mouse embryo.

The spatial and temporal aspects of cranial neural crest cell migration in the mouse are poorly understood because of technical limitations. No reliable cell markers are available and vital staining of embryos in culture has had limited success because they develop normally for only 24 hours. Here, we circumvent these problems by combining vital dye labelling with exo utero embryological techniques. To define better the nature of cranial neural crest cell migration in the mouse embryo, premigratory cranial neural crest cells were labelled by injecting DiI into the amniotic cavity on embryonic day 8. Embryos, allowed to develop an additional 1 to 5 days exo utero in the mother before analysis, showed distinct and characteristic patterns of cranial neural crest cell migration at the different axial levels. Neural crest cells arising at the level of the forebrain migrated ventrally in a contiguous stream through the mesenchyme between the eye and the diencephalon. In the region of the midbrain, the cells migrated ventrolaterally as dispersed cells through the mesenchyme bordered by the lateral surface of the mesencephalon and the ectoderm. At the level of the hindbrain, neural crest cells migrated ventrolaterally in three subectodermal streams that were segmentally distributed. Each stream extended from the dorsal portion of the neural tube into the distal portion of the adjacent branchial arch. The order in which cranial neural crest cells populate their derivatives was determined by labelling embryos at different stages of development. Cranial neural crest cells populated their derivatives in a ventral-to-dorsal order, similar to the pattern observed at trunk levels. In order to confirm and extend the findings obtained with exo utero embryos, DiI (1,1-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate) was applied focally to the neural folds of embryos, which were then cultured for 24 hours. Because the culture technique permitted increased control of the timing and location of the DiI injection, it was possible to determine the duration of cranial neural crest cell emigration from the neural tube. Cranial neural crest cell emigration from the neural folds was completed by the 11-somite stage in the region of the rostral hindbrain, the 14-somite stage in the regions of the midbrain and caudal hindbrain and not until the 16-somite stage in the region of the forebrain. At each level, the time between the earliest and latest neural crest cells to emigrate from the neural tube appeared to be 9 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Amnion↗
PubMed1995

Breathless, a Drosophila FGF receptor homolog, is required for the onset of tracheal cell migration and tracheole formation.

Breathless, a Drosophila FGF receptor homolog (DFGF-R1), was shown to be essential for the migration of the tracheal cells and the posterior midline glia cells. The temporal requirement for the activity of this receptor was dissected by a dominant-negative construct lacking a functional cytoplasmic tyrosine-kinase domain. Induction of the construct prior to the onset of tracheal or glial cell migration produced phenotypes that were similar to those observed in the corresponding tissues of breathless null mutant embryos. However, this effect is not detected if the dominant-negative receptor is induced after the initiation of tracheal cell migration, indicating that Breathless is required primarily at the onset of the migration process. Induction of the construct after the tracheal branches are completed, blocked the formation of tracheoles, i.e. extension of cellular processes by the terminal tracheal cells, demonstrating that Breathless plays an essential role in this process as well. The requirement for Breathless at the onset of migration and the diversity of processes in which it participates, suggest that the receptor is involved in triggering transcription factors, which may be distinct for each context.

Animals↗
PubMed2005

Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt.

Domain 5 (D5) of cleaved high molecular weight kininogen (HKa) inhibits angiogenesis in vivo and endothelial cell migration in vitro, but the cell signaling pathways involved in HKa and D5 inhibition of endothelial cell migration are incompletely delineated. This study examines the mechanism of HKa and D5 inhibition of two potent stimulators of endothelial cell migration, sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF), that act through the P13-kinase-Akt signaling pathway. HKa and D5 inhibit bovine pulmonary artery endothelial cell (BPAE) or human umbilical vein endothelial cell chemotaxis in the modified-Boyden chamber in response toVEGF or S1P. The inhibition of migration by HKa is reversed by antibodies to urokinase-type plasminogen activator receptor. Both HKa and D5 decrease the speed of BPAE cell migration and alter the morphology in live, time-lapse microscopy after stimulation with S1P or VEGF. HKa and D5 reduce the localization of paxillin to the focal adhesions after S1P and VEGF stimulation. To better understand the intracellular signaling pathways, we examined the effect of HKa on the phosphorylation of Akt and its downstream effector, GSK-3alpha HKa and D5 inhibit phosphorylation of Akt and GSK-3alpha after stimulation withVEGF and S1P. Inhibitors of Akt and P13-kinase, the upstream activator of Akt, block endothelial cell migration and disrupt paxillin localization to the focal adhesions after stimulation with VEGF and S1P. Therefore we suggest that HKa through its D5 domain alters P13-kinase-Akt signaling to inhibit endothelial cell migration through alterations in the focal adhesions.

Androstadienes↗
PubMed2001

Focal adhesion kinase regulates beta1 integrin-dependent T cell migration through an HEF1 effector pathway.

Although beta1 integrin-dependent T cell migration is required for immune function, little is known of the signaling pathways regulating this migration. We now show that the cytoplasmic tyrosine kinase, focal adhesion kinase (FAK) plays an essential role in the beta1 integrin-stimulated migration of T cells through regulation of the unique Crk-associated substrate (Cas) family docking protein, human enhancer of filamentation 1 (HEF1) and effects on "outside-in" beta1 integrin signaling. Overexpression of wild-type FAK promoted beta1 integrin-dependent Jurkat T cell migration, whereas FAK mutated in either its autophosphorylation site or proline rich region 1 (PR1)/HEF1 SH3 domain-binding site had a dominant negative effect on migration. In contrast, neither wild-type nor mutant FAK affected Jurkat cell adhesion to fibronectin, a beta1 integrin ligand. The migration of FAK-overexpressing cells directly correlated with the beta1 integrin-inducible tyrosine phosphorylation of endogenous plus wild-type exogenous FAK, and not with phosphorylation of the FAK-related kinase, Pyk2. FAK was also found to regulate both HEF1-promoted migration, and HEF1 tyrosine phosphorylation in beta1 integrin-stimulated cells, in a manner dependent upon the FAK autophosphorylation and PR1 sites, and HEF1 SH3 domain. Together, our results indicate that beta1 integrin-stimulated T cell migration requires a linear beta1 integrin-FAK-HEF1 effector pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Sphingosine 1-phosphate promotes cell migration through the activation of Cdc42 in Edg-6/S1P4-expressing cells.

BACKGROUND: Sphingosine 1-phosphate (Sph-1-P) is a bioactive lipid mediator released from activated platelets, which regulates diverse signal transduction pathways via cell surface receptors. Recent studies have revealed that the seven-transmembrane-spanning receptors, Edg-1, Edg-3, Edg-5, Edg-6 and Edg-8 are specific Sph-1-P receptors. Northern blot analysis has demonstrated that Edg-6 is expressed in lymphocyte-containing tissues such as spleen and lung. Little is known about the molecular mechanisms of Edg-6 functions, probably because of the difficulties in expressing Edg-6 on the cell surface. RESULTS: Here, our studies revealed that N-terminal FLAG-tagged Edg-6 or Edg-6-GFP fusion protein was expressed in the endoplasmic reticulum, but was not expressed on the cell surface. On the other hand, C-terminally tagged Edg-6 or both N-terminally and C-terminally tagged Edg-6 was able to localize to the cell surface. Using these cells, we found that Sph-1-P induced cell migration through cell surface-expressed Edg-6 in a pertussis toxin-sensitive manner. This motility was mediated through the activation of a member of the Rho family of small GTPases, Cdc42. CONCLUSION: These results support a role for Sph-1-P signalling via Edg-6 in the pathways involved in cell motility.

Animals↗
PubMedDate not supplied

Transition of aortic endothelial cells from resting to migrating cells is associated with three sequential patterns of microfilament organization.

The endothelial cell is unique because it must undergo a transition from a resting cell with a cytoskeleton organized for barrier function to one which promotes cell translocation following denuding endothelial injury. Since actin microfilaments are critical for both maintaining the integrity of the resting monolayer and for optimum reendothelialization, we carried out a detailed study of the organization of microfilaments as the cell undergoes the transition from a resting to a translocating cell. We used an in vitro model in which a linear wound was made in a confluent monolayer of porcine aortic endothelial cells. The complex reorganization of actin microfilament bundles following injury and their relationship to microtubules and vinculin was studied in cells at the wound edge using immunofluorescent scanning laser confocal microscopy and time-lapse videomicroscopy. In the resting confluent monolayer, microfilaments were present as a dense peripheral band (DPB) located toward the upper part of the cell and as central microfilament bundles at the substratum. Three distinct stages of microfilament reorganization occurred sequentially during early repair. Stage 1 followed wounding and involved the reduction of the DPBs of microfilaments and associated peripheral cell-cell vinculin plaques. This was associated with rapid forward actin-based lamellipodia extrusions and cell elongation. Low-dose cytochalasin, which did not disrupt the morphology of microfilament bundles, reduced elongation. Stage 2 was characterized by central microfilaments behind the lamellipodia distributed parallel to the wound edge with vinculin plaques at their tips. This was associated with prominent spreading at the front of the cell which enhanced the extent of coverage of the denuded wound area. Stage 3 was characterized by the orientation of central microfilaments perpendicular to the wound edge with vinculin plaques at their tips and was associated with the initiation of cell translocation. There was no specific structural association between central microfilaments and microtubules as the former were toward the substratum while the latter were toward the center and upper part of the cell. Thus, the sequential appearance of three patterns of microfilament distribution define the cytoskeletal events that regulate the reestablishment of endothelial integrity following denuding endothelial injury.

Actin Cytoskeleton↗
PubMed1987

Amphibian neural crest cell migration on purified extracellular matrix components: a chondroitin sulfate proteoglycan inhibits locomotion on fibronectin substrates.

The ability of purified extracellular matrix components to promote the initial migration of amphibian neural crest (NC) cells was quantitatively investigated in vitro. NC cells migrated avidly on fibronectin (FN), displaying progressively more extensive dispersion at increasing amounts of material incorporated in the substrate. In contrast, dispersion on laminin substrates was optimal at low protein concentrations but strongly reduced at high concentrations. NC cells were unable to migrate on substrates containing a high molecular mass chondroitin sulfate proteoglycan (ChSP). When proteolytic peptides, representing isolated functional domains of the FN molecule, were tested as potential migration substrates, the cell binding region of the molecule (105 kD) was found to be as active as the intact FN. A 31-kD heparin-binding fragment also stimulated NC cell migration, whereas NC cells dispersed to a markedly lower extent on the isolated collagen-binding domain (40 kD), or the latter domain linked to the NH2-terminal part of the FN molecule. Migration on the intact FN was partially inhibited by antibodies directed against the 105- and 31-kD fragments, respectively; dispersion was further decreased when the antibodies were used in combination. Addition of the ChSP to the culture medium dramatically perturbed NC cell migration on substrates of FN, as well as of 105- or 31-kD fragments. However, preincubation of isolated cells or substrates with ChSP followed by washing did not affect NC cell movement. The use of substrates consisting of different relative amounts of ChSP and the 105-kD peptide revealed that ChSP counteracted the motility-promoting activity of the 105-kD FN fragment in a concentration-dependent manner also when bound to the substrate. Our results indicate that NC cell migration on FN involves two separate domains of the molecule, and that ChSP can modulate the migratory behavior of NC cells moving along FN-rich pathways and may therefore influence directionally and subsequent localization of NC cells in the embryo.

Ambystoma↗
PubMed2005

[The effect of oxidative stress on retinal pigment epithelial cell migration].

OBJECTIVE: This study sought to determine if the migration and adhesion of retinal pigment epithelial (RPE) cell could be modulated by oxidative stress induced by t-butyl hydroperoxide (TBH). METHODS: Intracellular RPE reactive oxygen species (ROS) was labeled by Carboxy-H(2)DCFDA staining. Cell migration was measured by a modified Boyden Chamber Assay. After RPE cells were treated with different concentrations of TBH (1-200 micromol/L) for one hour, chemotaxis toward PDGF (30 ng/ml) was measured after additional 5 hours incubation. The actin cytoskeleton was evaluated by phalloidin (F-actin) staining. Focal adhesion kinase (FAK) and vinculin expression were evaluated using immunofluorescence staining. The expression of MAP Kinase and FAK were studied by western blot. Cell survival and attachment of treated RPE cells were determined using MTT assay. RESULTS: ROS production was elevated in the RPE cells pretreated with TBH. The PDGF-independent RPE cell migration was enhanced by TBH at low concentration up to 30 micromol/L, and the PDGF-induced RPE cell migration was significantly inhibited by TBH at concentration higher than 50 micromol/L. F-actin was aggregated in the periphery of the RPE cells after treatment with TBH at a dose higher than 100 micromol/L. FAK and vinculin expression in RPE cells decreased and their distribution were changed after the treatment of higher concentrations of TBH. MAP Kinase level was up-regulated in response to 10-200 micromol/L TBH exposure. The cell attachment was declined upon addition of TBH above 50 micromol/L. CONCLUSIONS: Oxidant stress induced by TBH can inhibit or promote RPE cell migration.

Cell Adhesion↗
PubMed2003

Border-cell migration: the race is on.

The conversion of stationary epithelial cells into migratory, invasive cells is important for normal embryonic development and tumour metastasis. Border-cell migration in the ovary of Drosophila melanogaster has emerged as a simple, genetically tractable model for studying this process. Three distinct signals, which are also upregulated in cancer, control border-cell migration, so identifying further genes that are involved in border-cell migration could provide new insights into tumour invasion.

Animals↗
PubMed2006

XHas2 activity is required during somitogenesis and precursor cell migration in Xenopus development.

In vertebrates, hyaluronan biosynthesis is regulated by three transmembrane catalytic enzymes denoted Has1, Has2 and Has3. We have previously cloned the Xenopus orthologues of the corresponding genes and defined their spatiotemporal distribution during development. During mammalian embryogenesis, Has2 activity is known to be crucial, as its abrogation in mice leads to early embryonic lethality. Here, we show that, in Xenopus, morpholino-mediated loss-of-function of XHas2 alters somitogenesis by causing a disruption of the metameric somitic pattern and leads to a defective myogenesis. In the absence of XHas2, early myoblasts underwent apoptosis, failing to complete their muscle differentiation programme. XHas2 activity is also required for migration of hypaxial muscle cells and trunk neural crest cells (NCC). To approach the mechanism whereby loss of HA, following XHas2 knockdown, could influence somitogenesis and precursor cell migration, we cloned the orthologue of the primary HA signalling receptor CD44 and addressed its function through an analogous knockdown approach. Loss of XCD44 did not disturb somitogenesis, but strongly impaired hypaxial muscle precursor cell migration and the subsequent formation of the ventral body wall musculature. In contrast to XHas2, loss of function of XCD44 did not seem to be essential for trunk NCC migration, suggesting that the HA dependence of NCC movement was rather associated with an altered macromolecular composition of the ECM structuring the cells' migratory pathways. The presented results, extend our knowledge on Has2 function and, for the first time, demonstrate a developmental role for CD44 in vertebrates. On the whole, these data underlie and confirm the emerging importance of cell-ECM interactions and modulation during embryonic development.

Animals↗
PubMed1990

Influence of the angiotensin system on endothelial and smooth muscle cell migration.

The blood vessel wall's response to injury is an important determinant of luminal size and vessel function. The physiologic migration of endothelial cells from the edges of a wound and the pathophysiologic migration of medial smooth muscle cells into the intima are two important components of the vessel wall's response to injury. The influence of the angiotensin system on endothelial and smooth muscle cell migration have not been examined. In the present study, the influence of angiotensin system components on bovine aortic endothelial cell (BAEC) and bovine aortic smooth muscle cell (BASMC) migration after release of cultured cell monolayers from contact inhibition was determined. The angiotensin-converting enzyme (ACE) inhibitor lisinopril increased BAEC migration 41% +/- 3% (P less than 0.001), as did the specific angiotensin II antagonist sar1, ile8-angiotensin II (SAR) (41% +/- 3% (P less than 0.001). Exogenous angiotensin I and angiotensin II did not affect BAEC migration. Exogenous angiotensin II abolished the effect of lisinopril on BAEC migration. Lisinopril increased cell-associated u-plasminogen activator (u-PA) 23% +/- 3% (P less than 0.001) in migrating BAEC and angiotensin II abolished this increase. SAR increased u-PA 33% +/- 0% (P less than 0.001). In contrast, these agents had the opposite effect on smooth muscle cells. Angiotensin II increased smooth muscle cell migration 40% +/- 3% (P less than 0.001), and this effect was abolished by SAR. Angiotensin II also increased cell-associated u-PA 83% +/- 7% (P less than 0.001) in migrating BASMC. The increase in BAEC migration with inhibition of endothelial cell angiotensin II stimulation, either with lisinopril or SAR, also was associated with an increase in cell-associated u-PA. These results indicate that lisinopril interrupts an autocrine pathway in endothelial cells, in which endothelial cell-derived angiotensin I is converted to angiotensin II by ACE, and imply that angiotensin-converting enzyme inhibitors in vivo would act to reduce vessel wall injury by directly increasing the rate of endothelial cell wound closure; by increasing the antithrombotic tendency of the endothelium via enhanced u-PA; and indirectly, by decreasing production of angiotensin II and thereby the rate of smooth muscle cell migration into the intima.

Angiotensins↗
PubMed1979

Cell-associated proteases affect tumour cell migration in vitro.

The in vitro migratory activity of mouse fibrosarcoma cells in medium containing either foetal calf serum or normal human serum was studied. These 2 sera were studied because foetal calf serum contains high levels of protease inhibitor activity while human serum contains much less. The cells migrated actively in medium with foetal calf serum but migration was greatly inhibited in human serum-containing medium. When protease inhibitors such as soybean trypsin inhibitor, lima bean trypsin inhibitor and bovine pancreas trypsin inhibitor were added to human serum-containing medium cell migration was supported almost as effectively as in medium with foetal calf serum. Addition of epsilon-amino-n-caproic acid to human serum or depletion of the plasminogen from human serum did not enable it to support enhanced migration. epsilon-amino-n-caproic acid actually inhibited migration. A variant cell population with elevated levels of caseinolytic activity and elevated levels of activity against the substrate n-acetyl-DL-phenylalanine-beta-naphthyl ester (a substrate specific for chymotrypsin-like enzymes) was isolated from the parent cells. When the variant cells were compared to the parent cells regarding migratory activity in foetal calf serum or human serum-containing medium, the variant cells showed much less activity. Only a few, widely scattered variant cells migrated in the human serum-containing medium. These data suggest that a cell-associated factor interferes with the migration of the cells in medium with human serum. This factor apparently is neutralized in medium sontaining human serum to which protease inhibitors with antitrypsin activity have been added.

Animals↗